Insights into the Mechanism of O(3P)-Mediated Oxidation of Alkenes through Kinetic Isotope Effects and Computational Modeling.

Photodeoxygenation of aryl sulfoxides, such as dibenzothiophene S-oxide (DBTO), produces atomic oxygen [O(3P)] in solution. The mechanism of alkene oxidation with O(3P) remains uncertain. To address this, the current study utilized kinetic isotope effects (KIEs) and computational approaches to study the reaction of O(3P) with styrene and its isotopologues. Notably, the 2° CH/D KIE at the internal and terminal carbons of the reactive π-bond was ∼1.00 and ∼0.87, respectively. These findings indicate a terminal addition of O(3P) to the π-bond, supporting a stepwise oxidation pathway. Both epoxide and aldehyde products go through the same rate-determining transition state and then diverge based on the intermediate conformation. The O-C-C-C dihedral angle (φ) on the triplet surface dictates the product distribution, where φ = 50° or 310° leads to epoxide formation and φ = 180° leads to aldehyde formation. Computational modeling suggests that the epoxide is formed through rapid ring closure upon intersystem crossing from the triplet to the singlet ground state. Similarly, the aldehyde is generated via a 1,2-H shift immediately following intersystem crossing. This study integrates experimental and computational methods to understand the O(3P)-mediated oxidation of alkenes, providing supporting evidence for a stepwise addition mechanism.

Comparison of Low-Density Lipoprotein Oxidation by Hydrophilic O(3 P)-Precursors and Lipid-O(3 P)-Precursor Conjugates.

Lipid oxidation by reactive oxygen species (ROS) provide several different oxidation products that have been implicated in inflammatory responses. Ground state atomic oxygen [O(3 P)] is produced by the photodeoxygenation of certain heterocyclic oxides and has a reactivity that is unique from other ROS. Due to the reactive nature of O(3 P), the site of O(3 P)-generation is expected to influence the products in heterogenous solutions or environments. In this work, the oxidation of low-density lipoprotein (LDL) by lipids with covalently bound O(3 P)-photoprecursors was compared to more hydrophilic O(3 P)-photoprecursors. Lipid oxidation products were quantified after Bligh-Dyer extraction and pentafluorobenzyl bromide (PFB) derivatization by GC-MS. Unlike the more hydrophilic O(3 P)-photoprecursors, the oxidation of LDL during the irradiation of lipid-(O3 P)-photoprecursor conjugates showed little quenching by the addition of the O(3 P)-scavenging sodium allyl sulfonate. This indicated that lipophilic O(3 P)-photoprecursors are expected to generate lipid oxidation products where other more hydrophilic O(3 P)-photoprecursors could be quenched by other reactive groups present in solution or the environment.

Photo-oxidation and Thermal Oxidations of Triptycene Thiols by Aryl Chalcogen Oxides.

Oxidation of thiols yield sulfenic acids, which are very unstable intermediates. As sulfenic acids are reactive, they form disulfides in the presence of thiols. However, sulfenic acids also oxidize to sulfinic acids (-SO2H) and sulfonic acids (-SO3H) at higher concentrations of oxidants. Hydrogen peroxide is a commonly used oxidant for the oxidation of thiols to yield sulfenic acids. However, hydrogen peroxide also oxidizes other reactive functional groups present in a molecule. In this work, the reaction intermediates arising from the oxidation of sterically hindered thiols by aryl chalcogen oxides, dibenzothiophene S-oxide (DBTO), dibenzoselenophene Se-oxide (DBSeO), and dibenzotellurophene Te-oxide (DBTeO), were investigated. Photodeoxygenation of DBTO produces triplet atomic oxygen [O(3P)], which has previously shown to preferentially react with thiols over other functional groups. Similarly, aryl selenoxides have also shown that they can thermally react selectively with thiols at room temperature to yield disulfides. Conversely, aryl telluroxides have been reported to oxidize thiols to disulfides thermally with no selectivity toward thiols. The results from this study demonstrate that sulfenic acids are an intermediate in the oxidation of thiols by DBTeO and by photodeoxygenation of DBTO. The results also showed that the oxidation of thiols by DBSeO yields sulfonic acids. Triptycene-9-thiol and 9-fluorotriptycene-10-thiol were for the thiols used in this oxidation reaction. This work expands the list of oxidants that can be used to oxidize thiols to obtain sulfenic acids.